Bile provides the major excretory route for cholesterol from the body, and optimum biliary cholesterol solubility and secretion are dependent on the phospholipid, lecithin. Although biliary lecithin originates in the liver, the pattern of individual molecular lecithins in bile is distinctly different than in whole liver or in plasma. Furthermore, although lecithin secretion is stimulated by bile salt, it is not known if selective lecithin secretion is the result of selective lecithin solubilization by bile salt, selective lecithin sybthesis in response to bile salt, or to localization of specific lecithins to a particular intrahepatic site. We have developed new High Performance liquid Chromatography methodology to separate and quantitate individual molecular lecithins. In studies proposed we shall first determine the constancy of biliary secretion of individual molecular lecithins (by comparing bile lecithins in different animal species and after pertubation of the enterohepatic circulation of bile salt). We next seek to identify the source of biliary lecithin by comparing the composition and turnover of specific molecular lecithins in isolated hepatic membranes (microsomes, canalicular, and non-canalicular plasma membranes) and bile, as well as by perfusing in vitro isolated hepatic membranes with bile salt and comparing the effluent phospholipid composition to the composition of bile. In all studies we shall relate the concentration of cholesterol to individual lecithins in bile, membranes, and perfused membrane effluents. Finally, we shall determine in vitro if cholesterol solubilization in mixed micelles is dependent on the component specific lecithins present. It is our expectation that the intrahepatic origin of the biliary mixed micelle can be traced using the distinct composition of bilary lecithins, that we can determine if cholesterol solubility and transport in bile requires particular kinds of lecithin, and that we can determine, if bile salts regulate biliary lecithin composition, the mechanism of this regulation. Our findings may provide a fuller understanding of the pathogenesis of cholesterol gallstone formation in humans, and may ultimately lead to gallstone dissolution therapy which is predicated in some part on changes in the composition of lecithin.